中文摘要：

纳米颗粒 （NPs） 目前被开发用于药物递送和分子成像。然而，它们经常在到达目标之前被拦截，导致瞄准效率和信噪比低下。它们往往会积聚在肺、肝、肾和脾脏等器官中。补救措施是迭代设计 NP 表面特性和给药策略，目前是一个耗时的过程，包括在不同时间点进行器官解剖。为了改善这一点，我们提出了一种快速迭代方法，使用全动物X射线荧光（XRF）成像来系统地评估体内NP分布。我们将这种方法应用于钼基NPs和氯膦酸盐脂质体（Clodronate Liposomes），用于肿瘤靶向与瞬时巨噬细胞耗竭，从而减少肺和肝脏中的积累并最终检测肿瘤。XRF 计算机断层扫描 （XFCT） 提供了肿瘤内 NP 分布的 3D 洞察。我们使用多尺度成像方法验证了结果，该方法具有染料掺杂的NPs和用于纳米毒理学分析的基因表达分析。XRF成像在推进临床前药代动力学研究中的治疗和诊断方面具有潜力。

Abstract

Nanoparticles (NPs) are currently developed for drug delivery and molecular imaging. However, they often get intercepted before reaching their target, leading to low targeting efficacy and signal-to-noise ratio. They tend to accumulate in organs like lungs, liver, kidneys, and spleen. The remedy is to iteratively engineer NP surface properties and administration strategies, presently a time-consuming process that includes organ dissection at different time points. To improve this, we propose a rapid iterative approach using whole-animal x-ray fluorescence (XRF) imaging to systematically evaluate NP distribution in vivo. We applied this method to molybdenum-based NPs and clodronate liposomes（Liposoma） for tumor targeting with transient macrophage depletion, leading to reduced accumulations in lungs and liver and eventual tumor detection. XRF computed tomography (XFCT) provided 3D insight into NP distribution within the tumor. We validated the results using a multiscale imaging approach with dye-doped NPs and gene expression analysis for nanotoxicological profiling. XRF imaging holds potential for advancing therapeutics and diagnostics in preclinical pharmacokinetic studies.

论文题目：Iterative nanoparticle bioengineering enabled by x-ray fluorescence imaging

期刊名称：SCIENCE ADVANCES

期卷日期：22 Mar 2024, Vol 10, Issue 12

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